{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:52:14Z","timestamp":1790189534035,"version":"4.1.0"},"reference-count":157,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341072"],"award-info":[{"award-number":["82341072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82341072"],"award-info":[{"award-number":["82341072"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key Laboratory of Molecular Virology","award":["20102209"],"award-info":[{"award-number":["20102209"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Enteroviruses represent important human pathogens, posing a substantial disease burden, particularly in children under 5 years of age. Enteroviruses are the primary causative agents of hand-foot-and-mouth disease (HFMD) and are strongly associated with acute flaccid myelitis (AFM), with severe cases potentially resulting in significant neurological complications. Inactivated vaccines against EV-A71 based on the C4 genotype are currently available. However, there are no licensed direct antiviral agents for severe cases. By focusing on viral proteins and host factors, researchers have made great strides in the creation of antiviral medications that target enteroviruses. However, several viral candidates failed to progress in clinical development due to limited efficacy or side effects. This review discusses key findings in enterovirus antiviral research, analyzes the advantages and limitations of each drug target, and highlights knowledge gaps that need to be addressed to advance further development in this field.<\/jats:p>","DOI":"10.3390\/v18040476","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advances in Antiviral Drug Development Targeting Enteroviruses: From Viral Proteins to Host Factors"],"prefix":"10.3390","volume":"18","author":[{"given":"Jiaying","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congyi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Geng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-521X","authenticated-orcid":false,"given":"Wenyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1099\/jgv.0.000911","article-title":"ICTV Virus Taxonomy Profile: Picornaviridae","volume":"98","author":"Zell","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1590\/s1678-9946201860070","article-title":"Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: A review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development","volume":"60","author":"Chang","year":"2018","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.meegid.2012.10.016","article-title":"Picornavirus and enterovirus diversity with associated human diseases","volume":"14","author":"Tapparel","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1423-0127-21-18","article-title":"Cell and tissue tropism of enterovirus 71 and other enteroviruses infections","volume":"21","author":"Lin","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12929-019-0573-2","article-title":"The History of Enterovirus A71 Outbreaks and Molecular Epidemiology in the Asia-Pacific Region","volume":"26","author":"Puenpa","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2589547","DOI":"10.1080\/22221751.2025.2589547","article-title":"Unveiling the enterovirus diversity in Barcelona, Spain (2020\u20132024) through wastewater and clinical surveillance","volume":"14","author":"Carcereny","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Xie, Z.F., Khamrin, P., Maneekarn, N., and Kumthip, K. (2024). Epidemiology of Enterovirus Genotypes in Association with Human Diseases. Viruses, 16.","DOI":"10.3390\/v16071165"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.7883\/yoken.JJID.2018.532","article-title":"An Epidemic of Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Osaka City, Japan, in 2017","volume":"72","author":"Kartbayashi","year":"2019","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"470","DOI":"10.7883\/yoken.JJID.2018.035","article-title":"Epidemiology Characteristics of Human Coxsackievirus A16 and Enterovirus 71 Circulating in Linyi, China, from 2009 to 2017","volume":"71","author":"Yin","year":"2018","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, Y., Yang, J.M., Liang, L., Wang, K., Turtle, L., Li, P., Zhou, Y.H., Shen, Y.F., Cui, P., and Zhou, C.C. (2025). Clinical characteristics and severity of hand, foot, and mouth disease by virus serotype: A prospective hospital-based cohort study. PLoS Negl. Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0013039"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1001\/jamaneurol.2015.4388","article-title":"Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children","volume":"73","author":"Teoh","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1186\/s13256-023-04041-6","article-title":"Enterovirus A71-associated acute flaccid paralysis in a pediatric patient: A case report","volume":"17","author":"Akinnurun","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s12985-025-02881-w","article-title":"Pilaralisib inhibits the replication of enteroviruses by targeting the PI3K\/AKT signaling pathway","volume":"22","author":"Zhou","year":"2025","journal-title":"Virol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1038\/s41586-025-08908-0","article-title":"MFSD6 is an entry receptor for enterovirus D68","volume":"641","author":"Varanese","year":"2025","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.virs.2022.11.004","article-title":"Diagnostic performance of different specimens in detecting enterovirus A71 in children with hand, foot and mouth disease","volume":"38","author":"Zhou","year":"2023","journal-title":"Virol. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ren, J.Y., Zhang, Z.F., Xia, Y., Zhao, D.Q., Li, D.Q., and Zhang, S.J. (2025). Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 Mpro. Molecules, 30.","DOI":"10.3390\/molecules30020351"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12250-018-0071-9","article-title":"Recent Progress on Functional Genomics Research of Enterovirus 71","volume":"34","author":"Wang","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Su, Y.S., Hsieh, P.Y., Li, J.S., Pao, Y.H., Chen, C.J., and Hwang, L.H. (2020). The Heat Shock Protein 70 Family of Chaperones Regulates All Phases of the Enterovirus A71 Life Cycle. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01656"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1016\/j.vaccine.2024.04.087","article-title":"Immunogenicity and immunodominant linear B-cell epitopes of a new DNA-based tetravalent vaccine against four major enteroviruses causing hand, foot, and mouth disease","volume":"42","author":"Bello","year":"2024","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, X.L., Zhang, Y.F., Li, H., and Liu, L.D. (2023). Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010169"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e0165524","DOI":"10.1128\/jvi.01655-24","article-title":"Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71","volume":"98","author":"Zhang","year":"2024","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nm.1992","article-title":"Scavenger receptor B2 is a cellular receptor for enterovirus 71","volume":"15","author":"Yamayoshi","year":"2009","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nm.1961","article-title":"Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71","volume":"15","author":"Nishimura","year":"2009","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11809","DOI":"10.1128\/JVI.00297-11","article-title":"Annexin II Binds to Capsid Protein VP1 of Enterovirus 71 and Enhances Viral Infectivity","volume":"85","author":"Yang","year":"2011","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1128\/JVI.02226-12","article-title":"Enterovirus 71 Uses Cell Surface Heparan Sulfate Glycosaminoglycan as an Attachment Receptor","volume":"87","author":"Tan","year":"2013","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1743-422X-6-141","article-title":"Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells","volume":"6","author":"Yang","year":"2009","journal-title":"Virol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1743-422X-11-47","article-title":"The molecule of DC-SIGN captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection","volume":"11","author":"Ren","year":"2014","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12929-019-0560-7","article-title":"Antivirals and vaccines for Enterovirus A71","volume":"26","author":"Lin","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1128\/AAC.43.9.2109","article-title":"Activity of pleconaril against enteroviruses","volume":"43","author":"Pevear","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.molmed.2024.06.011","article-title":"Virus as the cause of type 1 diabetes","volume":"30","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e70064","DOI":"10.1111\/irv.70064","article-title":"Emerging Therapeutics in the Fight Against EV-D68: A Review of Current Strategies","volume":"18","author":"Kalam","year":"2024","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7782","DOI":"10.1128\/AAC.01375-15","article-title":"Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68","volume":"59","author":"Sun","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7779","DOI":"10.1128\/AAC.00766-15","article-title":"In Vitro Efficacy of Antiviral Compounds against Enterovirus D68","volume":"59","author":"Rhoden","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105842","DOI":"10.1016\/j.antiviral.2024.105842","article-title":"The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants","volume":"224","author":"Ianevski","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.antiviral.2011.03.187","article-title":"Towards the design of combination therapy for the treatment of enterovirus infections","volume":"90","author":"Thibaut","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bcp.2011.08.016","article-title":"Combating enterovirus replication: State-of-the-art on antiviral research","volume":"83","author":"Thibaut","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105277","DOI":"10.1016\/j.ebiom.2024.105277","article-title":"Tanomastat exerts multi-targeted inhibitory effects on viral capsid dissociation and RNA replication in human enteroviruses","volume":"107","author":"Lim","year":"2024","journal-title":"EBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nsmb.2769","article-title":"More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules","volume":"21","author":"Wang","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105654","DOI":"10.1016\/j.antiviral.2023.105654","article-title":"Efficacy of an isoxazole-3-carboxamide analog of pleconaril in mouse models of Enterovirus-D68 and Coxsackie B5","volume":"216","author":"Lane","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1021\/acsinfecdis.0c00383","article-title":"Pharmacological Characterization of the Mechanism of Action of R523062, a Promising Antiviral for Enterovirus D68","volume":"6","author":"Ma","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9719","DOI":"10.1038\/s41598-021-89271-8","article-title":"Novel capsid binder and PI4KIIIbeta inhibitors for EV-A71 replication inhibition","volume":"11","author":"Tan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"116866","DOI":"10.1016\/j.biopha.2024.116866","article-title":"Magnolol against enterovirus 71 by targeting Nrf2-SLC7A11-GSH pathway","volume":"176","author":"Zhao","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Masomian, M., Lalani, S., and Poh, C.L. (2021). Molecular Docking of SP40 Peptide towards Cellular Receptors for Enterovirus 71 (EV-A71). Molecules, 26.","DOI":"10.3390\/molecules26216576"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Tan, C.W., Chan, Y.F., Sim, K.M., Tan, E.L., and Poh, C.L. (2012). Inhibition of Enterovirus 71 (EV-71) Infections by a Novel Antiviral Peptide Derived from EV-71 Capsid Protein VP1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034589"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e0043522","DOI":"10.1128\/jvi.00435-22","article-title":"Chemokine PF4 Inhibits EV71 and CA16 Infections at the Entry Stage","volume":"96","author":"Pei","year":"2022","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0185924","DOI":"10.1128\/jvi.01859-24","article-title":"Platelet factor 4-derived C15 peptide broadly inhibits enteroviruses by disrupting viral attachment","volume":"99","author":"Lv","year":"2025","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yang, X.Y., Aloise, C., van Vliet, A.L.W., Zwaagstra, M., Lyoo, H., Cheng, A.C., and van Kuppeveld, F.J.M. (2022). Proteolytic Activities of Enterovirus 2A Do Not Depend on Its Interaction with SETD3. Viruses, 14.","DOI":"10.3390\/v14071360"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e28400","DOI":"10.1002\/jmv.28400","article-title":"Phosphorylation of enteroviral 2Apro at Ser\/Thr125 benefits its proteolytic activity and viral pathogenesis","volume":"95","author":"Wang","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/jac\/dks304","article-title":"Blocking human enterovirus 71 replication by targeting viral 2A protease","volume":"67","author":"Falah","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/s41598-017-01110-x","article-title":"Antiviral activities of Schizonepeta tenuifolia Briq. against enterovirus 71 in vitro and in vivo","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e0078623","DOI":"10.1128\/jvi.00786-23","article-title":"Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease","volume":"97","author":"Zang","year":"2023","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.3390\/v7062764","article-title":"Antiviral Potential of a Novel Compound CW-33 against Enterovirus A71 via Inhibition of Viral 2A Protease","volume":"7","author":"Wang","year":"2015","journal-title":"Viruses"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ejmech.2013.07.053","article-title":"Synthesis and antiviral activity of a novel class of (5-oxazolyl)phenyl amines","volume":"69","author":"Zhong","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e0015623","DOI":"10.1128\/jvi.00156-23","article-title":"Telaprevir Treatment Reduces Paralysis in a Mouse Model of Enterovirus D68 Acute Flaccid Myelitis","volume":"97","author":"Frost","year":"2023","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e02221-18","DOI":"10.1128\/JVI.02221-18","article-title":"Validating Enterovirus D68-2Apro as an Antiviral Drug Target and the Discovery of Telaprevir as a Potent D68-2Apro Inhibitor","volume":"93","author":"Musharrafieh","year":"2019","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14544","DOI":"10.1021\/acs.jmedchem.3c00995","article-title":"Structure-Based Lead Optimization of Enterovirus D68 2A Protease Inhibitors","volume":"66","author":"Tan","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/cr.2011.112","article-title":"DIDS blocks a chloride-dependent current that is mediated by the 2B protein of enterovirus 71","volume":"21","author":"Xie","year":"2011","journal-title":"Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e0080123","DOI":"10.1128\/spectrum.00801-23","article-title":"CD74 Interacts with Proteins of Enterovirus D68 To Inhibit Virus Replication","volume":"11","author":"Xiang","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Yin, C.H., Zhao, H.M., Xia, X.Y., Pan, Z.Y., Li, D.Q., and Zhang, L.L. (2024). Picornavirus 2C proteins: Structure-function relationships and interactions with host factors. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1347615"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Shankar, K., Sorin, M.N., Sharma, H., Skoglund, O., Dahmane, S., ter Beek, J., Tesfalidet, S., Nenz\u00e9n, L., and Carlson, L.A. (2024). In vitro reconstitution reveals membrane clustering and RNA recruitment by the enteroviral AAA+ ATPase 2C. PLoS Pathog., 20.","DOI":"10.15252\/rc.2024452528"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1602573","DOI":"10.1126\/sciadv.1602573","article-title":"Crystal structure of 2C helicase from enterovirus 71","volume":"3","author":"Guan","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.1128\/AAC.00983-12","article-title":"Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication","volume":"56","author":"Zuo","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Lee, M.F., Tham, S.K., and Poh, C.L. (2025). Antiviral Strategies Targeting Enteroviruses: Current Advances and Future Directions. Viruses, 17.","DOI":"10.3390\/v17091178"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"E2118","DOI":"10.1212\/WNL.0000000000006670","article-title":"Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis","volume":"92","author":"Messacar","year":"2019","journal-title":"Neurology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1128\/AAC.02084-12","article-title":"Selective Serotonin Reuptake Inhibitor Fluoxetine Inhibits Replication of Human Enteroviruses B and D by Targeting Viral Protein 2C","volume":"57","author":"Ulferts","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bauer, L., Manganaro, R., Zonsics, B., Hurdiss, D.L., Zwaagstra, M., Donselaar, T., Welter, N.G.E., van Kleef, R., Lopez, M.L., and Bevilacqua, F. (2020). Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000904"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4074","DOI":"10.1021\/acs.jmedchem.9b00115","article-title":"Discovery of Quinoline Analogues as Potent Antivirals against Enterovirus D68 (EV-D68)","volume":"62","author":"Musharrafieh","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.virusres.2012.07.005","article-title":"Selection and characterisation of guanidine-resistant mutants of human enterovirus 71","volume":"169","author":"Sadeghipour","year":"2012","journal-title":"Virus Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1099\/0022-1317-81-4-895","article-title":"The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: The significance of viral protein 2C","volume":"81","author":"Klein","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1128\/JVI.01338-07","article-title":"The thiazolobenzimidazole TBZE-029 inhibits enterovirus replication by targeting a short region immediately downstream from motif C in the nonstructural protein 2C","volume":"82","author":"Heggermont","year":"2008","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1128\/AAC.02182-15","article-title":"Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C","volume":"60","author":"Ulferts","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"103981","DOI":"10.1016\/j.bioorg.2020.103981","article-title":"Development of broad-spectrum enterovirus antivirals based on quinoline scaffold","volume":"101","author":"Musharrafieh","year":"2020","journal-title":"Bioorganic Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"112310","DOI":"10.1016\/j.ejmech.2020.112310","article-title":"Identification of dibucaine derivatives as novel potent enterovirus 2C helicase inhibitors: In vitro, in vivo, and combination therapy study","volume":"202","author":"Tang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1021\/acs.jmedchem.7b01863","article-title":"Synthesis and Structure-Activity Relationship (SAR) Studies of Novel Pyrazolopyridine Derivatives as Inhibitors of Enterovirus Replication","volume":"61","author":"Xing","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1038\/s41467-025-61083-8","article-title":"A rationally designed 2C inhibitor prevents enterovirus D68-infected mice from developing paralysis","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Li, D.Q., and Zhang, L.L. (2022). Structure Prediction and Potential Inhibitors Docking of Enterovirus 2C Proteins. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.856574"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e02324-20","DOI":"10.1128\/JVI.02324-20","article-title":"Antiviral Peptides Targeting the Helicase Activity of Enterovirus Nonstructural Protein 2C","volume":"95","author":"Fang","year":"2021","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Li, X.H., Wang, M.S., Cheng, A.C., Wen, X.J., Ou, X.M., Mao, S., Gao, Q., Sun, D., Jia, R.Y., and Yang, Q. (2020). Enterovirus Replication Organelles and Inhibitors of Their Formation. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01817"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e0174923","DOI":"10.1128\/jvi.01749-23","article-title":"N-terminal acetyltransferase 6 facilitates enterovirus 71 replication by regulating PI4KB expression and replication organelle biogenesis","volume":"98","author":"Yang","year":"2024","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e00791-17","DOI":"10.1128\/JVI.00791-17","article-title":"Enterovirus 3A Facilitates Viral Replication by Promoting Phosphatidylinositol 4-Kinase III\u03b2-ACBD3 Interaction","volume":"91","author":"Xiao","year":"2017","journal-title":"J. Virol."},{"key":"ref_81","first-page":"3375","article-title":"PI4KIII inhibitor enviroxime impedes the replication of the hepatitis C virus by inhibiting PI3 kinases","volume":"73","author":"Delang","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1128\/JVI.02249-10","article-title":"Phosphatidylinositol 4-Kinase III Beta Is a Target of Enviroxime-Like Compounds for Antipoliovirus Activity","volume":"85","author":"Arita","year":"2011","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.antiviral.2017.01.008","article-title":"Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307","volume":"140","author":"Albulescu","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1016\/j.bmcl.2016.04.002","article-title":"Purine analogs as phosphatidylinositol 4-kinase III\u03b2 inhibitors","volume":"26","author":"Hrebabecky","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1021\/acsinfecdis.7b00053","article-title":"Allosteric Regulation of Phosphatidylinositol 4-Kinase Ill Beta by an Antipicornavirus Compound MDL-860","volume":"3","author":"Arita","year":"2017","journal-title":"ACS Infect. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1055\/s-0042-112970","article-title":"Effectiveness of the Consecutive Alternating Administration Course of a Triple Antiviral Combination in Coxsackievirus B3 Infections in Mice","volume":"66","author":"Galabov","year":"2016","journal-title":"Drug Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e0055223","DOI":"10.1128\/spectrum.00552-23","article-title":"Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type III\u03b2","volume":"11","author":"Laajala","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"106021","DOI":"10.1016\/j.antiviral.2024.106021","article-title":"Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells","volume":"231","author":"Butrym","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1002\/jmv.70009","article-title":"Macrophages can transmit coxsackievirus B4 to pancreatic cells and can impair these cells","volume":"96","author":"Vergez","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105713","DOI":"10.1016\/j.antiviral.2023.105713","article-title":"CUR-N399, a PI4KB inhibitor, for the treatment of Enterovirus A71 infection","volume":"218","author":"Cheong","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.antiviral.2015.02.013","article-title":"Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP","volume":"117","author":"Albulescu","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3892\/ol.2025.15107","article-title":"OSW-1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma","volume":"30","author":"Shen","year":"2025","journal-title":"Oncol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1128\/AAC.05108-14","article-title":"Discovery of Itraconazole with Broad-Spectrum In Vitro Antienterovirus Activity That Targets Nonstructural Protein 3A","volume":"59","author":"Gao","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"104548","DOI":"10.1016\/j.antiviral.2019.104548","article-title":"Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds","volume":"170","author":"Roberts","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e0068623","DOI":"10.1128\/jvi.00686-23","article-title":"Foot-and-Mouth Disease Virus Induces Porcine Gasdermin E-Mediated Pyroptosis through the Protease Activity of 3Cpro","volume":"97","author":"Ren","year":"2023","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1021\/acsinfecdis.5c00680","article-title":"Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases","volume":"12","author":"Brimble","year":"2025","journal-title":"ACS Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6060","DOI":"10.1080\/14786419.2022.2043308","article-title":"Geraniin as a potential inhibitor of SARS-CoV-2 3CLpro","volume":"36","author":"Yu","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.apsb.2021.08.017","article-title":"Enterovirus A71 antivirals: Past, present, and future","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Le, T.T.V., and Do, P.C. (2022). Molecular docking study of various Enterovirus-A71 3C protease proteins and their potential inhibitors. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.987801"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jare.2023.03.007","article-title":"Advances in anti-EV-A71 drug development research","volume":"56","author":"Wang","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10319","DOI":"10.1128\/JVI.00787-11","article-title":"Enterovirus 71 and Coxsackievirus A16 3C Proteases: Binding to Rupintrivir and Their Substrates and Anti-Hand, Foot, and Mouth Disease Virus Drug Design","volume":"85","author":"Lu","year":"2011","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1107\/S2052252525008929","article-title":"Structural insights into the antiviral efficacy of AG7404 against human rhinovirus 3C proteases","volume":"13","author":"Lee","year":"2026","journal-title":"IUCrJ"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.antiviral.2013.03.003","article-title":"Anti-poliovirus activity of protease inhibitor AG-7404, and assessment of in vitro activity in combination with antiviral capsid inhibitor compounds","volume":"98","author":"Rhoden","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00018-025-05581-4","article-title":"Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures","volume":"82","author":"Ravlo","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ejmech.2016.08.064","article-title":"Structure\u2013activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors","volume":"124","author":"Zhai","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e00298-17","DOI":"10.1128\/AAC.00298-17","article-title":"Structure of the Enterovirus 71 3C Protease in Complex with NK-1.8k and Indications for the Development of Antienterovirus Protease Inhibitor","volume":"61","author":"Wang","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6990","DOI":"10.1128\/AAC.03328-14","article-title":"The Capsid Binder Vapendavir and the Novel Protease Inhibitor SG85 Inhibit Enterovirus 71 Replication","volume":"58","author":"Tijsma","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1128\/JVI.01123-12","article-title":"3C Protease of Enterovirus 68: Structure-Based Design of Michael Acceptor Inhibitors and Their Broad-Spectrum Antiviral Effects against Picornaviruses","volume":"87","author":"Tan","year":"2013","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9414","DOI":"10.1021\/acs.jmedchem.5b01013","article-title":"Cyanohydrin as an Anchoring Group for Potent and Selective Inhibitors of Enterovirus 71 3C Protease","volume":"58","author":"Zhai","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10333","DOI":"10.1021\/acs.jmedchem.8b01335","article-title":"4-Iminooxazolidin-2-one as a Bioisostere of the Cyanohydrin Moiety: Inhibitors of Enterovirus 71 3C Protease","volume":"61","author":"Ma","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e0102521","DOI":"10.1128\/Spectrum.01025-21","article-title":"4-Iminooxazolidin-2-One as a Bioisostere of Cyanohydrin Suppresses EV71 Proliferation by Targeting 3Cpro","volume":"9","author":"Xu","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.ejmech.2016.10.019","article-title":"Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening","volume":"124","author":"Ma","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"11754","DOI":"10.1128\/JVI.01348-12","article-title":"Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses","volume":"86","author":"Kim","year":"2012","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"115551","DOI":"10.1016\/j.bmc.2020.115551","article-title":"Design, synthesis, and evaluation of a novel macrocyclic anti-EV71 agent","volume":"28","author":"Li","year":"2020","journal-title":"Bioorganic Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12985-018-1023-6","article-title":"Inhibition of enterovirus 71 replication and viral 3C protease by quercetin","volume":"15","author":"Yao","year":"2018","journal-title":"Virol. J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"106185","DOI":"10.1016\/j.antiviral.2025.106185","article-title":"Peptides designed based on 3C substrates exhibit antiviral efficacy in vivo","volume":"239","author":"Liu","year":"2025","journal-title":"Antivir. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"100298","DOI":"10.1016\/j.labinv.2023.100298","article-title":"Recent Advances in Enterovirus A71 Infection and Antiviral Agents","volume":"104","author":"Wei","year":"2024","journal-title":"Lab. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e00204-20","DOI":"10.1128\/JVI.00204-20","article-title":"The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses","volume":"94","author":"Xu","year":"2020","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1038\/s41598-023-29517-9","article-title":"Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro","volume":"13","author":"Radoshitzky","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/cid\/ciaf111","article-title":"A Systematic Review and Meta-analysis of the Effectiveness of Remdesivir to Treat Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Patients: Have the Guidelines Evolved With the Evidence?","volume":"81","author":"Bartoletti","year":"2025","journal-title":"Clin. Infect. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ye, W., Yao, M., Dong, Y.C., Ye, C.T., Wang, D., Liu, H., Ma, H.W., Zhang, H., Qi, L.B., and Yang, Y.W. (2020). Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.621197"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1177\/13524585251322327","article-title":"Severe coxsackie virus B5 encephalitis mimics autoimmune limbic encephalitis in a young woman under long-term B-cell depletion with ocrelizumab: A case report","volume":"31","author":"Schegerer","year":"2025","journal-title":"Mult. Scler. J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e00487-17","DOI":"10.1128\/JVI.00487-17","article-title":"Understanding the Mechanism of the Broad-Spectrum Antiviral Activity of Favipiravir (T-705): Key Role of the F1 Motif of the Viral Polymerase","volume":"91","author":"Abdelnabi","year":"2017","journal-title":"J. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"11915","DOI":"10.1128\/JVI.01207-14","article-title":"Inhibition of Enterovirus 71 by Adenosine Analog NITD008","volume":"88","author":"Deng","year":"2014","journal-title":"J. Virol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1128\/AAC.00101-09","article-title":"Novel Antiviral Agent DTriP-22 Targets RNA-Dependent RNA Polymerase of Enterovirus 71","volume":"53","author":"Chen","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"van der Linden, L., Vives-Adri\u00e1n, L., Selisko, B., Ferrer-Orta, C., Liu, X.R., Lanke, K., Ulferts, R., De Palma, A.M., Tanchis, F., and Goris, N. (2015). The RNA Template Channel of the RNA-Dependent RNA Polymerase as a Target for Development of Antiviral Therapy of Multiple Genera within a Virus Family. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004733"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.antiviral.2014.10.003","article-title":"BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71","volume":"112","author":"Velu","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/jac\/dkp502","article-title":"Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid","volume":"65","author":"Hung","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.antiviral.2017.07.001","article-title":"Antiviral effects of Retro-2cycl and Retro-2.1 against Enterovirus 71 in vitro and in vivo","volume":"144","author":"Dai","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e0035823","DOI":"10.1128\/mbio.00358-23","article-title":"Advances and Breakthroughs in IRES-Directed Translation and Replication of Picornaviruses","volume":"14","author":"Abdullah","year":"2023","journal-title":"mBio"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Martinez-Salas, E., Francisco-Velilla, R., Fernandez-Chamorro, J., and Embarek, A.M. (2018). Insights into Structural and Mechanistic Features of Viral IRES Elements. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02629"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"104650","DOI":"10.1016\/j.antiviral.2019.104650","article-title":"Emetine protects mice from enterovirus infection by inhibiting viral translation","volume":"173","author":"Tang","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e242315","DOI":"10.1148\/radiol.242315","article-title":"Idarubicin versus Epirubicin in Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma: An Open-label, Randomized, Phase IV Trial","volume":"315","author":"Liu","year":"2025","journal-title":"Radiology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1099\/jgv.0.000431","article-title":"Idarubicin is a broad-spectrum enterovirus replication inhibitor that selectively targets the virus internal ribosomal entry site","volume":"97","author":"Hou","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.virusres.2012.06.025","article-title":"In vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against Enterovirus 71","volume":"169","author":"Pourianfar","year":"2012","journal-title":"Virus Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eaar5759","DOI":"10.1126\/scitranslmed.aar5759","article-title":"Prunin suppresses viral IRES activity and is a potential candidate for treating enterovirus A71 infection","volume":"11","author":"Gunaseelan","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"105755","DOI":"10.1016\/j.antiviral.2023.105755","article-title":"Licochalcone A regulates viral IRES activity to inhibit enterovirus replication","volume":"221","author":"Chuang","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Dai, W.W., Bi, J.P., Li, F., Wang, S., Huang, X.Y., Meng, X.Y., Sun, B., Wang, D.L., Kong, W., and Jiang, C.L. (2019). Antiviral Efficacy of Flavonoids against Enterovirus 71 Infection in Vitro and in Newborn Mice. Viruses, 11.","DOI":"10.3390\/v11070625"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.1038\/s41467-020-18594-3","article-title":"IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex","volume":"11","author":"Patwardhan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1093\/jac\/dkq381","article-title":"Primary resistance to maraviroc in a large set of R5-V3 viral sequences from HIV-1-infected patients","volume":"65","author":"Lapaz","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.antiviral.2017.12.010","article-title":"Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses","volume":"150","author":"Schulte","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"117047","DOI":"10.1016\/j.biopha.2024.117047","article-title":"Silvestrol, a potent anticancer agent with unfavourable pharmacokinetics: Current knowledge on its pharmacological properties and future directions for the development of novel drugs","volume":"177","author":"Peron","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Too, I.H.K., Bonne, I., Tan, E.L., Chu, J.J.H., and Alonso, S. (2018). Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006778"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"eaba7910","DOI":"10.1126\/sciadv.aba7910","article-title":"Viruses harness Yxxempty set motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target","volume":"6","author":"Yuan","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"131453","DOI":"10.1016\/j.ijbiomac.2024.131453","article-title":"Inhibition of ESCRT-independent extracellular vesicles biogenesis suppresses enterovirus 71 replication and pathogenesis in mice","volume":"267","author":"Liang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s11262-025-02141-7","article-title":"Study of Hsp90\u03b1 and Hsp90\u03b2 role in virus replication using cell lines with Hsp90 gene knockouts","volume":"61","author":"Bieganowski","year":"2025","journal-title":"Virus Genes"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.3390\/v7082832","article-title":"Replication and Inhibitors of Enteroviruses and Parechoviruses","volume":"7","author":"Wolthers","year":"2015","journal-title":"Viruses"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1021\/acs.jmedchem.9b00091","article-title":"Discovery, Optimization, and Target Identification of Novel Potent Broad-Spectrum Antiviral Inhibitors","volume":"62","author":"Yang","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"105498","DOI":"10.1016\/j.antiviral.2022.105498","article-title":"ML390 inhibits enterovirus 71 replication by targeting de novo pyrimidine biosynthesis pathway","volume":"209","author":"Yang","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_150","first-page":"8247","article-title":"Brequinar inhibits enterovirus replication by targeting biosynthesis pathway of pyrimidines","volume":"12","author":"Fu","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1083\/jcb.201107058","article-title":"Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export","volume":"196","author":"Zhang","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"107711","DOI":"10.1016\/j.ijantimicag.2025.107711","article-title":"Regorafenib, a multitargeted kinase inhibitor, inhibits enterovirus 71 infection by suppressing the MAPK pathway","volume":"67","author":"Zhang","year":"2026","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e01060-18","DOI":"10.1128\/JVI.01060-18","article-title":"CVB3 Nonstructural 2A Protein Modulates SREBP1a Signaling via the MEK\/ERK Pathway","volume":"92","author":"Wang","year":"2018","journal-title":"J. Virol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"190ra79","DOI":"10.1126\/scitranslmed.3005471","article-title":"FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection","volume":"5","author":"Johansen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Jurgeit, A., McDowell, R., Moese, S., Meldrum, E., Schwendener, R., and Greber, U.F. (2012). Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002976"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s12985-025-02966-6","article-title":"Antiviral candidates for enterovirus 71: Targeting viral proteome and stage-specific lifecycle interventions","volume":"22","author":"Chen","year":"2025","journal-title":"Virol. J."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrd4333","article-title":"Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery","volume":"13","author":"Torchilin","year":"2014","journal-title":"Nat. Rev. Drug Discov."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/476\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:03:18Z","timestamp":1776758598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":157,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["v18040476"],"URL":"https:\/\/doi.org\/10.3390\/v18040476","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]}}}